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    THE REGULATORY ROLES OF GAMMA INTERFERON INDUCIBLE LYSOSOMAL THIOL REDUCTASE (GILT) IN CELLULAR REDOX HOMEOSTASIS

    Cover for THE REGULATORY ROLES OF GAMMA INTERFERON INDUCIBLE LYSOSOMAL THIOL REDUCTASE (GILT) IN CELLULAR REDOX HOMEOSTASIS
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    View/Open: Chiang_georgetown_0076D_11309.pdf (21.MB) Bookview

    Creator
    Chiang, Hao-Sen
    Advisor
    Maric, Maja
    Abstract
    Redox regulation is critical for a number of cellular functions and has been implicated in the etiology and progression of cardiovascular diseases, neurodegenerative diseases, and cancer. It has been shown that in the absence of Gamma-interferon Inducible Lysosomal Thiol reductase (GILT), cells experience moderate oxidative stress indicated by increased production of reactive oxygen species and reduced expression of mitochondrial manganese superoxide dismutase (SOD2). In the current study, we further elucidate the role of GILT in homeostatic regulation in response to oxidative stress. We show that GILT-deficient fibroblasts exhibit a decreased level of reduced glutathione, an increase in the ratio of oxidized (GSSG) vs. reduced (GSH) forms of glutathione and an accumulation of dysfunctional mitochondria. Redox-sensitive pathways involving Erk1/2 activation and high mobility group box 1 (HMGB1) protein cytosolic translocation are both activated and associated with an increased autophagy in GILT -/- fibroblasts. We hypothesize that the absence of GILT triggers these intracellular changes that ultimately result in the degradation of the damaged mitochondria and mitochondrial SOD2 in the absence of GILT. To our knowledge, this is the first time that a lysosomal enzyme has been implicated in maintenance of cellular redox homeostasis.
    Description
    Ph.D.
    Permanent Link
    http://hdl.handle.net/10822/558137
    Date Published
    2011
    Subject
    Autophagy; GILT; glutathione; redox; ROS; SOD2; Immunology; Cytology; Biochemistry; Immunology; Cellular Biology; Biochemistry;
    Type
    thesis
    Embargo Lift Date
    2015-05-17
    Publisher
    Georgetown University
    Extent
    128 leaves
    Collections
    • Graduate Theses and Dissertations - Microbiology & Immunology
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    Georgetown University Seal
    ©2009 - 2022 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility